Cocaine is a commonly abused euphoriant with strong reinforcing effects. Animal data have shown that the reinforcing properties are related to cocaine's activity on the dopamine system. We designed a Positron Emission Tomography study to investigate cocaine's activity in humans on regional cerebral flow in dopaminergically innervated and comparison regions. Four subjects were injected with O15 water 30 to 180 seconds after cocaine injection. All subjects reported subjective euphoriant effects on Visual Analog Scales. Global cerebral blood flow was reduced 32(8% in all subjects. Maximal decreases were seen 60 seconds after cocaine injection. We demonstrated that doses of cocaine similar to typical "street doses" reduce global blood flow acutely. Further analyses, once adequate subject numbers are available, will yield data on local changes.